{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:05:54Z","timestamp":1786982754096,"version":"build-2736575974"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1007\/s40262-023-01328-1","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T06:40:10Z","timestamp":1705560010000},"page":"241-253","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacokinetics, Disposition, and Biotransformation of [14C]Lenacapavir, a Novel, First-in-Class, Selective Inhibitor of HIV-1 Capsid Function, in Healthy Participants Following a Single Intravenous Infusion"],"prefix":"10.1007","volume":"63","author":[{"given":"Elijah","family":"Weber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Graupe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Begley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wolckenhauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rhee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Palaparthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3512-1288","authenticated-orcid":false,"given":"Renu","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"1328_CR1","unstructured":"UNAIDS. 2021 Global HIV Statistics. Fact Sheet\u2014June, 2021. [cited 2022 March 11]. https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"1328_CR2","unstructured":"HIV.gov. U. S. Statistics. [cited 2022 March 11]. https:\/\/www.hiv.gov\/hiv-basics\/overview\/data-and-trends\/statistics."},{"issue":"8","key":"1328_CR3","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41577-021-00649-1","volume":"22","author":"NL Board","year":"2022","unstructured":"Board NL, Moskovljevic M, Wu F, Siliciano RF, Siliciano JD. Engaging innate immunity in HIV-1 cure strategies. Nat Rev Immunol. 2022;22(8):499\u2013512.","journal-title":"Nat Rev Immunol"},{"issue":"19","key":"1328_CR4","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1056\/NEJMoa2115542","volume":"386","author":"S Segal-Maurer","year":"2022","unstructured":"Segal-Maurer S, DeJesus E, Stellbrink H-J, Castagna A, Richmond GJ, Sinclair GI, et al. Capsid inhibition with lenacapavir in multidrug-resistant HIV-1 infection. N Engl J Med. 2022;386(19):1793\u2013803.","journal-title":"N Engl J Med"},{"key":"1328_CR5","unstructured":"Daar ES, McDonald C, Crofoot G, Ruane P, Sinclair G, Patel H, et al. Safety and antiviral activity over 10 days following a single dose of subcutaneous GS-6207, a first-in-class, long-acting HIV capsid inhibitor in people living with HIV. IAS; Abstract LBPEB13; 2019."},{"key":"1328_CR6","unstructured":"Yant SR, Mulato A, Stepan G, Villasenor AG, Jin D, Margot NA, et al. GS-6207, a potent and selective first-in-class long-acting HIV-1 capsid inhibitor. In: Conference on retroviruses and opportunistic infections; Seattle, Washington. Abstract 480; 2019."},{"key":"1328_CR7","doi-asserted-by":"crossref","unstructured":"Zheng J, Yant SR, Ahmadyar S, Chan TY, Chiu A, Cihlar T, et al. 539. GS-CA2: a novel, potent, and selective first-in-class inhibitor of HIV-1 capsid function displays nonclinical pharmacokinetics supporting long-acting potential in humans. Open Forum Infect Dis. 2018;5(Suppl 1):S199\u2013S200.","DOI":"10.1093\/ofid\/ofy210.548"},{"issue":"6514","key":"1328_CR8","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1126\/science.abb4808","volume":"370","author":"SM Bester","year":"2020","unstructured":"Bester SM, Wei G, Zhao H, Adu-Ampratwum D, Iqbal N, Courouble VV, et al. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020;370(6514):360\u20134.","journal-title":"Science"},{"issue":"7822","key":"1328_CR9","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1038\/s41586-020-2443-1","volume":"584","author":"JO Link","year":"2020","unstructured":"Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584(7822):614\u20138.","journal-title":"Nature"},{"key":"1328_CR10","unstructured":"Begley R, Lutz J, Rhee M, Dvory-Sobol H, Chiu A, West SK, et al. GS-6207 sustained delivery formulation supports 6-month dosing interval. In: AIDS; Virtual. Abstract 8533; Poster PEB0265; 2020."},{"key":"1328_CR11","unstructured":"Sager JE, Begley R, Rhee M, West SK, Ling J, Schroeder SD, et al. Safety and PK of subcutaneous GS-6207, a novel HIV-1 capsid inhibitor. In: Conference in retroviruses and opportunistic infections; Seattle, Washington. Abstract 141; 2019."},{"key":"1328_CR12","unstructured":"Gilead Sciences I. Sunlenca (lenacapavir) [package insert]. 2023."},{"key":"1328_CR13","unstructured":"Molina J-M, SoranaSegal-Maurer, Stellbrink H-J, Castagna A, MezgebeBerhe, Richmond G, et al. Efficacy and safety of long-acting subcutaneous lenacapavirin phase 2\/3 in heavily treatment-experienced people with HIV: week 26 results (CAPELLA study). In: IAS conference on HIV science. 2021; Abstract 2605."},{"key":"1328_CR14","unstructured":"Ogbuagu O, Segal-Maurer S, Brinson C, Chetchotisakd P, Lichtenstein K, McGowan J, et al. Long-acting lenacapavir in people with multidrug resistant HIV-1: week 52 results. In: Conference on retroviruses and opportunistic infections; Virtual; Abstract 491; February 12\u201316; 2022."},{"key":"1328_CR15","unstructured":"ClinicalTrials.gov. A phase 2\/3 study to evaluate the safety and efficacy of long acting capsid inhibitor GS-6207 in combination with an optimized background regimen in heavily treatment experienced people living with HIV-1 infection with multidrug resistance. [cited 2022 March 11]. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04150068."},{"key":"1328_CR16","unstructured":"New Clinical Data Support the Sustained Efficacy of Long-acting Lenacapavir, Gilead\u2019s Investigational HIV-1 Capsid Inhibitor. [cited 2022 March 11]. https:\/\/www.gilead.com\/news-and-press\/press-room\/press-releases\/2022\/2\/new-clinical-data-support-the-sustained-efficacy-of-longacting-lenacapavir-gileads-investigational-hiv1-capsid-inhibitor."},{"key":"1328_CR17","unstructured":"Gilead Sciences I. Sunlenca (lenacapavir) Summary of Product Characteristics. 2023."},{"key":"1328_CR18","unstructured":"ClinicalTrials.gov. [NCT04143594] Study to evaluate the safety and efficacy of lenacapavir in combination with other antiretroviral agents in people living with HIV (CALIBRATE)."},{"key":"1328_CR19","unstructured":"FDA. Clinical Pharmacology Considerations for Human Radiolabeled Mass Balance Studies Guidance for Industry. 2022."},{"key":"1328_CR20","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for industry estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Rockville. 2005."},{"key":"1328_CR21","unstructured":"National Institute of Allergy and Infectious Diseases. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Corrected Version 2.1 July 2017. [cited 2022 March 11]. https:\/\/rsc.niaid.nih.gov\/sites\/default\/files\/daidsgradingcorrectedv21.pdf."},{"key":"1328_CR22","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. 2021 [cited 2022 September 21]. https:\/\/clinicalinfo.hiv.gov\/sites\/default\/files\/guidelines\/documents\/AdultandAdolescentGL.pdf."},{"key":"1328_CR23","doi-asserted-by":"crossref","unstructured":"Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009 Apr 10;58(Rr-4):1\u2013207; quiz CE1\u20134.","DOI":"10.1037\/e537722009-001"},{"issue":"11","key":"1328_CR24","doi-asserted-by":"publisher","first-page":"2567","DOI":"10.1111\/cts.13403","volume":"15","author":"A Ramamoorthy","year":"2022","unstructured":"Ramamoorthy A, Bende G, Chow ECY, Dimova H, Hartman N, Jean D, et al. Human radiolabeled mass balance studies supporting the FDA approval of new drugs. Clin Transl Sci. 2022;15(11):2567\u201375.","journal-title":"Clin Transl Sci"},{"key":"1328_CR25","doi-asserted-by":"crossref","unstructured":"Zheng J, Tse W, Lu B, Mwangi J, Rowe W, Schroeder S, et al. Intestinal excretion is a major disposition pathway of lenacapavir in rat and dog. FASEB J. 2021;35.","DOI":"10.1096\/fasebj.2021.35.S1.00423"},{"key":"1328_CR26","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c00626","author":"R Subramanian","year":"2023","unstructured":"Subramanian R, Tang J, Zheng J, Lu B, Wang K, Yant SR, et al. Lenacapavir: a novel, potent and selective first-in-class inhibitor of HIV-1 capsid function exhibits optimal pharmacokinetic properties for a long-acting injectable antiretroviral agent. Mol Pharm. 2023. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.3c00626.\u00a0Epub ahead of print. PMID: 37917742.","journal-title":"Mol Pharm"},{"key":"1328_CR27","doi-asserted-by":"crossref","unstructured":"Zheng J, Yant SR, Ahmadyar S, Chan TY, Chiu A, Cihlar T, et al. 539. GS-CA2: a novel, potent, and selective first-in-class inhibitor of HIV-1 capsid function displays nonclinical pharmacokinetics supporting long-acting potential in humans. Open Forum Infect Dis. 2018;5(Suppl 1):S199\u2013200.","DOI":"10.1093\/ofid\/ofy210.548"},{"key":"1328_CR28","unstructured":"Jogiraju V, Begley R, Hindman J, West SK, Ho E, Ling J, German P. Pharmacokinetics of lenacapavir, an HIV-1 capsid inhibitor, in hepatic impairment. In: Conference on retroviruses and opportunistic infections; 2021."},{"key":"1328_CR29","unstructured":"FDA. Guidance for Industry\u2014Pharmacokinetics in Patients with Impaired Renal Function\u2014Study Design, Data Analysis, and Impact on Dosing and Labeling. 2010."},{"key":"1328_CR30","unstructured":"Weber EJ, Graham H, West SK, Ling J, Rhee M, Palaparthy R. Pharmacokinetics of lenacapavir in participants with severe renal impairment. In: Conference on retroviruses and opportunistic infections; 2022."}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-023-01328-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-023-01328-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-023-01328-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T06:06:13Z","timestamp":1707199573000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-023-01328-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,18]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["1328"],"URL":"https:\/\/doi.org\/10.1007\/s40262-023-01328-1","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,18]]},"assertion":[{"value":"12 November 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2024","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Funding for this project and involved analyses was provided by Gilead Sciences, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"All authors are\/were employees and\/or shareholders of Gilead Sciences, Inc. at the time of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was conducted in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice and was approved by the institutional review board.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Each participant provided written informed consent before any study-related procedures were performed.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors provided consent for publication.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code availability"}},{"value":"Conceptualization: EW, RS, WR, MG, JL, RB, JS, SW, MR. Formal analysis and investigation: EW, RS, WR, JL, GS, RB, JS, SW, MR, RP, RS. Writing: All authors read, commented, and approved the previous or final version of the manuscript.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}},{"value":"Gilead Sciences shares anonymized individual patient data upon request or as required by law or regulation with qualified external researchers based on submitted curriculum vitae and reflecting no conflict of interest. The request proposal must also include a statistician. Approval of such requests is at Gilead Science's discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to datarequest@gilead.com.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data sharing"}}]}}